A multimodal approach combining cognitive assessment with biomarkers may accurately predict dementia risk

1. Plasma p-tau217 was the strongest individual biomarker for predicting progression to Alzheimer’s disease dementia in patients with subjective cognitive decline.

2. A multimodal model combining cognitive assessment, plasma p-tau217, and APOE4 genotype provided excellent prognostic accuracy and may support early risk stratification in memory clinic populations.

Evidence Rating Level: 2 (Good)

This longitudinal observational study evaluated the prognostic utility of clinical, plasma, and imaging biomarkers for predicting cognitive decline in individuals with subjective cognitive decline (SCD) from the BioFINDER-1 and BioFINDER-2 cohorts. SCD is increasingly recognized as a preclinical stage of Alzheimer’s disease (AD), yet optimal risk stratification remains uncertain. The investigators included 469 participants with SCD (mean age 69.1 years; 51.4% female) who underwent baseline cognitive testing, APOE genotyping, plasma phosphorylated tau (p-tau217) measurement, and MRI assessment of cortical thickness, hippocampal volume, and white matter hyperintensity burden. Cox proportional hazards models were used to assess progression to all-cause dementia, AD dementia, and mild cognitive impairment (MCI). Over a mean follow-up of 4.0 years, 84 participants progressed to dementia, two-thirds of whom developed AD dementia. Progressors demonstrated worse baseline cognition, higher plasma p-tau217 levels, greater cortical and hippocampal atrophy, and higher white matter disease burden. Plasma p-tau217 was the strongest single predictor of AD dementia (C-index 0.86), while multimodal models incorporating cognition, plasma p-tau217, and APOE4 status achieved excellent predictive accuracy (C-index 0.91). MRI markers provided only marginal additional value for AD prediction, but improved prediction of all-cause dementia. The authors conclude that a clinically feasible multimodal approach combining cognitive testing, plasma p-tau217, and APOE4 status can accurately identify individuals with SCD at the highest risk for future dementia, particularly AD dementia.

Click here to read the study in Neurology

Image: PD

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